Venlafaxine, (±)-1-[2-(dimethylamino)-1-(4-ethyoxyphenyl)ethyl]cyclo-hexanol, having the following formula I, is the first of a class of anti-depressants. Venlafaxine acts by inhibiting re-uptake of norepinephrine and serotonin, and is an alternative to the tricyclic anti-depressants and selective re-uptake inhibitors.

O-Desmethylvenlafaxine, chemically named 4-[2-(dimethylamino)-1-(1-hydroxycyclohexyl)ethyl]phenol and having the following formula II
is a major metabolite of venlafaxine and has been shown to inhibit norepinephrine and serotonin uptake. Klamerus, K. J. et al., “Introduction of the Composite Parameter to the Pharmacokinetics of Venlafaxine and its Active O-Desmethyl Metabolite”, J. Clin. Pharmacol. 32:716-724 (1992).
O-Desmethylvenlafaxine and processes for preparation thereof are described in U.S. Pat. Nos. 6,197,828 and 6,689,912, and in US 2005/0197392, all of which are incorporated herein by reference.
The fumarate salt of O-desmethylvenlafaxine, is chemically named -[2-(dimethyl-amino)-1-(4-phenol)ethyl]-cyclohexanol fumarate, and has the following formula III

Several pharmaceutically acceptable salts of O-desmethylvenlafaxine are described in U.S. Pat. No. 4,535,186. In Example 26 of this reference, a preparation of the fumarate salt is described. The product is reported to have a melting point range of 140° C.-142° C. WO2009070311 describes two pure polymorphic forms of O-desmethylvenlafaxine fumarate, Forms I and II. WO2009101458 discloses an amorphous form of O-desmethylvenlafaxine fumarate, and four polymorphic forms: Forms I, II, amorphous, III and Form IV.
Polymorphism, the occurrence of different crystal forms, is a property of some molecules and molecular complexes. A single molecule, like O-desmethylvenlafaxine, may give rise to a variety of polymorphs having distinct crystal structures and physical properties like melting point, thermal behaviours (e.g. measured by thermogravimetric analysis—“TGA”, or differential scanning calorimetry—“DSC”), X-ray diffraction (XRD) pattern, infrared absorption fingerprint, and solid state NMR spectrum. One or more of these techniques may be used to distinguish different polymorphic forms of a compound.
Discovering new polymorphic forms and solvates of a pharmaceutical product can provide materials having desirable processing properties, such as ease of handling, ease of processing, storage stability, and ease of purification or as desirable intermediate crystal forms that facilitate conversion to other polymorphic forms. New polymorphic forms and solvates of a pharmaceutically useful compound or salts thereof can also provide an opportunity to improve the performance characteristics of a pharmaceutical product. It enlarges the repertoire of materials that a formulation scientist has available for formulation optimization, for example by providing a product with different properties, e.g., better processing or handling characteristics, improved dissolution profile, or improved shelf-life. For at least these reasons, there is a need for additional polymorphs of O-desmethylvenlafaxine and O-desmethylvenlafaxine salts.
The present invention comprises new solid state forms of O-desmethylvenlafaxine fumarate salt.